Genetic Variant MTAP:c.120+82_120+85dupAAAA (chr9-21815590-T-TAAAA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_002451.4(MTAP):c.120+82_120+85dupAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0073 ( 14 hom., cov: 0)

Exomes 𝑓: 0.021 ( 1 hom. )

Consequence

MTAP
NM_002451.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.529

Variant links:

Genes affected

MTAP (HGNC:7413): (methylthioadenosine phosphorylase) This gene encodes an enzyme that plays a major role in polyamine metabolism and is important for the salvage pathway of both adenine and methionine. The encoded enzyme is deficient in many cancers. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2021]

MTAP links:

ENSG00000264545 (HGNC:):

ENSG00000264545 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00735 (1075/146280) while in subpopulation AFR AF = 0.0232 (923/39760). AF 95% confidence interval is 0.022. There are 14 homozygotes in GnomAd4. There are 489 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 1075 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4 link	c.120+82_120+85dupAAAA		intron_variant	Intron 2 of 7	ENST00000644715.2	NP_002442.2	Q13126-1A0A384ME80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2 link	c.120+82_120+85dupAAAA		intron_variant	Intron 2 of 7		NM_002451.4	ENSP00000494373.1		Q13126-1

Frequencies

GnomAD3 genomes

AF:

0.00735

AC:

1075

AN:

146222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0233

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00100

Gnomad SAS

AF:

0.000650

Gnomad FIN

AF:

0.00162

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.00802

GnomAD2 exomes

AF:

0.0105

AC:

900

AN:

85622

AF XY:

0.00989

show subpopulations

Gnomad AFR exome

AF:

0.0225

Gnomad AMR exome

AF:

0.0137

Gnomad ASJ exome

AF:

0.00792

Gnomad EAS exome

AF:

0.0156

Gnomad FIN exome

AF:

0.00431

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.0214

AC:

13067

AN:

609392

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

6555

AN XY:

324582

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0359

AC:

465

AN:

12954

American (AMR)

AF:

0.0195

AC:

389

AN:

19942

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

280

AN:

17360

East Asian (EAS)

AF:

0.0193

AC:

528

AN:

27298

South Asian (SAS)

AF:

0.0114

AC:

602

AN:

53018

European-Finnish (FIN)

AF:

0.0133

AC:

576

AN:

43424

Middle Eastern (MID)

AF:

0.0164

AC:

AN:

2376

European-Non Finnish (NFE)

AF:

0.0237

AC:

9567

AN:

403378

Other (OTH)

AF:

0.0209

AC:

621

AN:

29642

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.304

Heterozygous variant carriers

1241

2481

3722

4962

6203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00735

AC:

1075

AN:

146280

Hom.:

Cov.:

AF XY:

0.00690

AC XY:

489

AN XY:

70846

show subpopulations

African (AFR)

AF:

0.0232

AC:

923

AN:

39760

American (AMR)

AF:

0.00366

AC:

AN:

14740

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00100

AC:

AN:

4994

South Asian (SAS)

AF:

0.000654

AC:

AN:

4588

European-Finnish (FIN)

AF:

0.00162

AC:

AN:

8652

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000882

AC:

AN:

66894

Other (OTH)

AF:

0.00843

AC:

AN:

2016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

104

155

207

259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0199

Hom.:

233

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Loading publications...

chr9-21815590-T-TAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over